Significant progress is being made toward prevention and cures for many human diseases via swine-based research. Unfortunately, there are several major impediments to the realization of the full potential of pigs as models of human disease. The overall goal for this application is to establish a National Swine Research and Resource Center (NSRRC), which will address these major impediments. The proposed NSRRC will develop the infrastructure to ensure that biomedical investigators across a variety of disciplines have access to critically needed swine models of human health and disease. The NSRRC will also serve as a central resource for reagents, information and training related to swine models. An interdisciplinary team of scientists exists at the MU with experience in establishing and operating successful animal resource centers and each of the disciplines required to operate the NSRRC. No other place in the country possesses this array of skills and resources. The Specific Aims are: 1. To develop a National Swine Research and Resource Center. Functions of the NSRRC will include: (a) Importation of existing swine models of human health and disease, (b) rederivation of pigs to eliminate pathogens and health monitoring to assure maintenance of a pathogen-free status, (c) cryopreservation and storage of gametes, embryos and somatic cells to prevent future loss of valuable models, (d) distribution of high quality, pathogen-free pigs, and (e) creation of genetically-engineered pigs. 2. To perform innovative research that will benefit the NSRRC and the biomedical research community. Research projects are aimed at improving: a) the cryopreservation of pig reproductive cells and tissues; and b) the detection and elimination of microbial pathogens in pigs, reproductive cells and tissues; and c) development of improved methods for the production of transgenic and knockout pigs. The NSRRC will also serve as a site for training and educational activities related to research employing swine models.